A number of new analogs of cAMP have been found to inhibit the growth of cultured H35 hepatoma cells. Three types of effects have been obtained: 1) partial, reversible inhibition of growth; 2) complete, reversible inhibition and 3) irreversible inhibition. Only one analog, N6-benzylamino cAMP, exerts type 2 effects and is also a potent enzyme inducer and protein kinase activator. Four cAMP analogs, 8 NH2, 8- NHCH2H4OH, 6-SH and 6-SCH3 exert type 3 effects. We plan to compare the effects of these two groups of analogs on DNA, RNA and protein synthesis in randomly growing cells. The time of exposure of cells to type 3 analogs required to produce irreversible effects will be determined. Cells will also be exposed to type 2 and 3 analogs in serum-free medium or during a thymidine block to determine whether cells must be in the process of replication to be irreversibly affected. Possible incorporation of the 5' nucleotide of each analog into RNA and/or DNA will be assessed initially in cells grown in Pi32. Alkaline hydrolysis of RNA and DNase II digestion of DNA should transfer P32 to any analog incorporated which can be identified chromatographically. Small-scale animal studies will be initiated to see if these analogs are also effective inhibitors of solid tumor growth.